Faith Avritt
Pronouns: she/her
Research Mentor(s): Yaqing Zhang
Co-Presenter:
Research Mentor School/College/Department: Surgery / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Faith Avritt, Yaqing Zhang
Presenter: 85
Abstract
Background: There are numerous genes involved with tumor regulation that impact the level of immune cells present in the tumor microenvironment. Understanding the relationship between these genes with the tumor microenvironment provides potential therapeutic targets to improve the anti-tumor immunity to control the tumor growth. The high-expression of gene C-C chemokine receptor type 1 (CCR1) appears to be associated with tumor associated macrophages in pancreatic cancer, one of the deadly malignancies in the Unite States, so this research aims to understand the role of CCR1 gene in pancreatic cancer. Methods: To evaluate the effects of targeting CCR1 in pancreatic cancer models, orthotopic transplantation of mouse pancreatic ductal adenocarcinoma cells were performed to generate pancreatic cancer in CCR1 knockout (CCR1-/-) mice. The tumors harvested from these mice were stained by co-immunofluorescent (IF) staining to show Arginase 1 (Arg1) expression in F4/80+ macrophages. Other methods include bone marrow extraction from the CCR1-/- and wild-type (WT) mice for in vitro cell culture in cancer conditioned media to establish bone marrow derived macrophages (BMDM). The BMDM cells were harvested for mRNA and later used for RT-qPCR to further look at the gene expression for immunosuppressive genes such as Arg1. Results: qPCR data demonstrated a decrease in Arg1 gene expression in BMDM derived from CCR1 -/- mice in comparison to that from WT mice. There has also been notice of a decrease in orthotopic tumor growth in CCR1 -/- mice in comparison to WT mice. Co-IF staining confirmed that Arg1 expression was decreased at the protein level in tumor associated macrophages when CCR1 gene was knocked out in vivo. Conclusion: CCR1 gene plays an important role in the tumor microenvironment of pancreatic cancer. Targeting CCR1 led to impaired tumor growth in an orthotopic mouse model of pancreatic cancer, partially through down-regulation of immunosuppressive molecule Arg1 in tumor associated macrophages. This research opens doors to further evaluate the function of CCR1 in tumor microenvironment, especially the possibility of CCR1 as a therapeutic target to help human patients.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
